The objective of the proposed research is to isolate and characterize selected cell surface proteins of thymus-dependent (T) and thymus-independent (B) lymphocytes in order to provide basic knowledge which will contribute to an understanding of their different immunological functions. These studies will also provide basic knowledge which will be used to develop a rational approach towards the manipulation of the immune system using antisera directed against lymphocyte surface antigens. This may be of therapeutic value in an immunological approach to the treatment of malignant diseases. Our initial studies have identified mouse T and B cell-specific plasma membrane proeins by selective labelling of cell surface components using lactoperoxidase catalyzed radioiodination. These proteins are the major iodinated species precipitated by rabbit anti-mouse lymphocyte serum suggesting they are the major cell surface antigens recognized by rabbit anti-mouse lymphocyte antibodies. We will isolate and characterize these proteins after solubilization of the proteins in neutral or weakly ionic detergents using standard procedures. We will search for other cell surface differences between mouse T and B cells, using other selective cell surface labelling procedures and by immunological techniques. Using the procedures developed in the mouse system, we will identify and characterize differences in the cell surfaces of human T and B cells. finally, we propose to attempt to develop a specific binding assay which can be operated in the presence of detergent to identify the T cell antigen receptor.